Infection of 3T3 cells by the DNA tumor virus, SV40, results in induction of cellular DNA synthesis, integration of the viral genome into cellular DNA and neoplastic transformation. It is proposed to study the relationship among these processes by isolating 3T3 cellular mutants resistant to the induction of cellular DNA synthesis by SV40 and test them for their susceptibility to neoplastic transformation and ability to integrate the viral genome. Mutant cells must be selected by exposing SV40-infected confluent cultures to conditions which are selectively lethal for DNA synthesizing cells. Mutants will be used to identify cellular genes involved in regulation of normal DNA synthesis. Somatic cell hybridization techniques will be used to study dominance relationships between wild type and mutant alleles and to carry out pair-wise complementation tests among mutant strains.